Array level Fourier ptychographic imaging

• US 9,829,695 B2
• Filed: 01/26/2016
• Issued: 11/28/2017
• Est. Priority Date: 01/26/2015
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Kim, Jinho, Yang, Changhuei
• Primary Examiner(s): Porta, David
• Assistant Examiner(s): BOOSALIS, FANI POLYZOS
• Application Number:
  US15/007,196
• Publication Number:
  US 20160216503A1
• Time in Patent Office: 672 Days
• CPC Class Codes: G01N 2021/6478 Special lenses
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 2201/0446 Multicell plate, sequential
• CPC Class Codes: G02B 13/0095 Relay lenses or rod lenses in instruments for viewing the inside of hollow bodies G02B23/2446
• CPC Class Codes: G02B 21/0076 arrangements using fluorescence or luminescence
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/365 Control or image processing arrangements for digital or video microscopes G02B21/361, G02B21/362 take precedence
• CPC Class Codes: G02B 21/367 providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
• CPC Class Codes: H04N 23/45 for generating image signals from two or more image sensors being of different type or operating in different modes, e.g. with a CMOS sensor for moving images in combination with a charge-coupled device [CCD] for still images
• CPC Class Codes: H04N 23/56 provided with illuminating means
• CPC Class Codes: H04N 23/957 Light-field or plenoptic cameras or camera modules

Abstract

In one aspect an imaging system includes: an illumination system including an array of light sources; an optical system including one or more lens arrays, each of the lens arrays including an array of lenses, each of the lenses in each of the one or more lens arrays in alignment with a corresponding set of light sources of the array of light sources; an imaging system including an array of image sensors, each of the image sensors in alignment with a corresponding lens or set of lenses of the one or more lens arrays, each of the image sensors configured to acquire image data based on the light received from the corresponding lens or set of lenses; a plate receiver system capable of receiving a multi-well plate including an array of wells, the plate receiver system configured to align each of the wells with a corresponding one of the image sensors; and a controller configured to control the illumination of the light sources and the acquisition of image data by the image sensors, the controller further configured to perform: an image acquisition process including a plurality of scans, each scan associated with a unique pattern of illumination, each of the image sensors configured to generate an image for a respective one of the wells during each scan; and an image reconstruction process during which the controller performs a fourier ptychographic operation to generate a reconstructed image for each of the wells based on the image data captured for the respective well during each of the scans.

Claims

1. A Fourier ptychographic imaging system comprising:

an illumination system including an array of light sources;

a plate receiver system configured to receive a multi-well sample plate including an array of sample wells, and to align the multi-well sample plate with the array of light sources such that each sample well is capable of receiving light from a corresponding plurality of the light sources;

an optical system including at least one array of lenses, each lens configured to receive light from a corresponding sample well;

an imaging system including an array of image sensors, each image sensor configured to receive light from a corresponding lens and to acquire image data based on the received light; and

a controller configured to;

cause, for each scan of a plurality of scans, the illumination system to illuminate the array of sample wells in parallel and such that each of the sample wells is illuminated with light at an angle of incidence different than in the other scans of the plurality of scans;

cause, for each scan of the plurality of scans, the image sensors to acquire image data for the respective sample wells in parallel based on the illumination; and

perform a Fourier ptychographic operation to generate a reconstructed image for each of the sample wells based on the image data acquired for the respective sample well from the plurality of scans.

2. The imaging system of claim 1, wherein:

the plurality of scans includes n scans; and

the controller is configured to cause the illumination system to illuminate the array of sample wells such that each of the sample wells is illuminated with light at n different angles of incidence over the n respective scans.

3. The imaging system of claim 2, wherein the corresponding plurality of the light sources associated with each sample well includes n light sources, each of the n light sources being aligned with a different respective angle of incidence.

4. The imaging system of claim 1, wherein each of the sample wells is illuminated by one and only one light source during each scan.

5. The imaging system of claim 1, wherein each of the sample wells is illuminated by two or more light sources during at least one scan of the plurality of scans.

6. The imaging system of claim 1, wherein the plate receiver system is configured to align the multi-well plate between the illumination system and the optical system such that each of the sample wells is aligned with and between the corresponding plurality of the light sources and a corresponding set of one or more lenses of the at least one array of lenses.

7. The imaging system of claim 1, wherein the lenses of the at least one array of lenses are configured to focus light scattered by samples in the sample wells onto the respective image sensors.

8. The imaging system of claim 1, wherein the controller performs the Fourier ptychographic operation to generate the reconstructed images for the respective sample wells in parallel.

9. The imaging system of claim 1, wherein the Fourier ptychographic operation includes an aberration correction operation capable of correcting for aberrations.

10. The imaging system of claim 1, wherein the controller is further configured to:

cause the illumination system to illuminate the array of sample wells in parallel with excitation light configured to excite fluorophores;

cause the image sensors to acquire fluorescent image data for the respective sample wells in parallel based on light emitted by excited fluorophores in the array of sample wells; and

generate a fluorescent image for each of the sample wells in parallel based on the fluorescent image data acquired for the respective sample well.

11. The imaging system of claim 10, further comprising a filter configured to filter light at an excitation light wavelength and to pass light at an emitted light wavelength.

12. The imaging system of claim 1, wherein the controller is further configured to perform a calibration operation to determine values of the angles of incidence of the light that will illuminate each of the sample wells over the plurality of scans.

13. A method for performing Fourier ptychographic imaging comprising:

illuminating, by an array of light sources, for each scan of a plurality of scans, an array of sample wells in parallel and such that each of the sample wells is illuminated with light at an angle of incidence different than in the other scans of the plurality of scans;

acquiring, by an array of image sensors, for each scan of the plurality of scans, image data for the array of sample wells in parallel based on the illumination, wherein each image sensor is configured to receive light from a corresponding lens of an array of lenses and each lens is configured to receive light from a corresponding sample well; and

performing a Fourier ptychographic operation to generate a reconstructed image for each of the sample wells in parallel based on the image data acquired for the respective sample well from the plurality of scans, wherein the reconstructed image has higher resolution than the acquired image data.

14. The method of claim 13, wherein:

the plurality of scans includes n scans; and

each of the sample wells is illuminated with light at n different angles of incidence over the n respective scans.

15. The method of claim 14, wherein each of the sample wells is illuminated by n light sources over the plurality of scans, each of the n light sources being aligned with a different respective angle of incidence.

16. The method of claim 13, wherein each of the sample wells is illuminated by one and only one light source during each scan.

17. The method of claim 13, wherein each of the sample wells is illuminated by two or more light sources during at least one scan of the plurality of scans.

18. The method of claim 13, further comprising performing an aberration correction operation capable of correcting for aberrations.

19. The method of claim 13, further comprising:

illuminating the array of sample wells in parallel with excitation light configured to excite fluorophores;

acquiring fluorescent image data for the respective sample wells in parallel based on light emitted by excited fluorophores in the array of sample wells; and

generating a fluorescent image for each of the sample wells in parallel based on the fluorescent image data acquired for the respective sample well.

20. The method of claim 13, further comprising performing a calibration operation to determine the values of the angles of incidence of the light that will illuminate each of the sample wells over the plurality of scans.